Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

POST-TRANSCRIPTIONAL CONTROLS
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Figure 7–56 Five patterns of alternative RNA splicing. In each case, a
single type of RNA transcript is spliced in two alternative ways to produce
two distinct mRNAs (1 and 2). The dark blue boxes mark exon sequences
that are retained in both mRNAs. The light blue boxes mark possible exon
sequences that are included in only one of the mRNAs. The boxes are
joined by red lines to indicate where intron sequences (yellow) are removed.
(Adapted from H. Keren et al. Nat. Rev. Genet. 11:345–355, 2010. With
permission from Macmillan Publishers Ltd.)
Riboswitches are perhaps the most economical examples of gene control
devices, inasmuch as they bypass the need for regulatory proteins altogether. In
the example shown in Figure 7–55, the riboswitch controls transcription elongation,
but they can also regulate other steps in gene expression, as we shall see later
in this chapter. Clearly, highly sophisticated gene control devices can be made
from short sequences of RNA, a fact that supports the hypothesis of an early “RNA
world.”
Alternative RNA Splicing Can Produce Different Forms of a Protein
from the Same Gene
As discussed in Chapter 6 (see Figure 6–26), RNA splicing shortens the transcripts
of many eukaryotic genes by removing the intron sequences from the mRNA precursor.
We also saw that a cell can splice an RNA transcript differently and thereby
make different polypeptide chains from the same gene—a process called alternative
RNA splicing (Figure 7–56). A substantial proportion of animal genes (estimated
at 90% in humans) produce multiple proteins in this way.
When different splicing possibilities exist at several positions in the transcript,
a single gene can produce dozens of different proteins. In one extreme case, a
Drosophila gene may produce as many as 38,000 different proteins from a single
gene through alternative splicing (Figure 7–57), although only a fraction of these
forms have thus far been experimentally observed. Considering that the Drosophila
genome has approximately 14,000 identified genes, it is clear that the protein
complexity of an organism can greatly exceed the number of its genes. This example
also illustrates the perils in equating gene number with an organism’s complexity.
For example, alternative splicing is rare in single-celled budding yeasts
1
2
1
2
1
2
1
2
1
2
exon skipping
intron retention
alternative 5′ splice site
alternative 3′ splice site
mutually exclusive exons
MBoC6 m7.94/7.57
A exons B exons C exons D exons
1 12 1 48 1
33 12
Dscam gene
A8
C16
mRNA
B24
Figure 7–57 Alternative splicing of RNA transcripts of the Drosophila Dscam gene. DSCAM proteins have several different functions. In cells
of the fly immune system, they mediate the phagocytosis of bacterial pathogens. In cells of the nervous system, DSCAM proteins are needed for
proper wiring of neurons. The final mRNA contains 24 exons, four of which (denoted A, B, C, and D) are present in the Dscam gene as arrays of
alternative exons. Each RNA contains 1 of 12 alternatives for exon A (red), 1 of 48 alternatives for exon B (green), 1 of 33 alternatives for exon C
(blue), and 1 of 2 alternatives for exon D (yellow). This figure shows only one of the many possible splicing patterns (indicated by the red line and
by the mature mRNA below it). Each variant DSCAM protein would fold into roughly the same structure (predominantly a series of extracellular
immunoglobulin-like domains linked to a membrane-spanning region; see Figure 24–48), but the amino acid sequence of the domains vary
according to the splicing pattern. The diversity of DSCAM variants contributes to the plasticity of the immune system as well as the formation of
complex neural circuits; we take up the specific role of the DSCAM MBoC6 variants m7.95/7.58 in more detail when we describe the development of the nervous system
in Chapter 21. (Adapted from D.L. Black, Cell 103:367–370, 2000. With permission from Elsevier.)
D2
one out of 38,016 possible splicing patterns